Safety and immunogenicity of a heterologous prime-boost Ebola virus vaccine regimen in healthy adults in the United Kingdom and Senegal

Abstract

Background The 2014 West African outbreak of Ebola virus disease highlighted the urgent need to develop an effective Ebola vaccine. Methods We undertook two Phase I studies assessing safety and immunogenicity of the viral vector MVA-EBO-Z, manufactured rapidly on a new duck cell line either alone or in a heterologous prime-boost regimen with ChAd3-EBO-Z followed by MVA-EBO-Z. Adult volunteers in the UK (n = 38) and Senegal (n=40) were vaccinated and an accelerated one week prime-boost regimen was assessed in Senegal. Safety was assessed by active and passive collection of local and systemic adverse events. Results The standard and accelerated heterologous prime-boost regimes were well-tolerated and elicited potent cellular and humoral immunogenicity in the UK and Senegal, but vaccine-induced antibody responses were significantly lower in Senegal. Cellular immune responses measured by flow cytometry were significantly greater in African vaccinees receiving ChAd3 and MVA vaccines in the same rather than the contralateral limb. Conclusions MVA biomanufactured on an immortalised duck cell line shows potential for very large-scale manufacturing with lower cost of goods. This first trial of MVA-EBO-Z in humans encourages further testing in Phase II studies with the one week prime-boost interval regimen appearing particularly suitable for outbreak control

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